We shall continue studies on the pathogenesis of Creutzfeldt-Jakob disease in convenient laboratory animals. The possible occurrence of strains of the Creutzfeldt-Jakob agent will be investigated using various genotypes of hamsters. We shall continue our fractionation and EM studies to elucidate the maximal locus of infectivity and response to the agent within CNS cells. Our experiments with tissue cultures arising from infected brains will continue. In a timed experiment with guinea pigs we shall investigate with the EM the first appearance of ultrastructural changes in the brain.